The dietary management of calcium and phosphate in children with CKD stages 2-5 and on dialysis-clinical practice recommendation from the Pediatric Renal Nutrition Taskforce.

In children with chronic kidney disease (CKD), optimal control of bone and mineral homeostasis is essential, not only for the prevention of debilitating skeletal complications and achieving adequate growth but also for preventing vascular calcification and cardiovascular disease. Complications of mineral bone disease (MBD) are common and contribute to the high morbidity and mortality seen in children with CKD. Although several studies describe the prevalence of abnormal calcium, phosphate, parathyroid hormone, and vitamin D levels as well as associated clinical and radiological complications and their medical management, little is known about the dietary requirements and management of calcium (Ca) and phosphate (P) in children with CKD. The Pediatric Renal Nutrition Taskforce (PRNT) is an international team of pediatric renal dietitians and pediatric nephrologists, who develop clinical practice recommendations (CPRs) for the nutritional management of various aspects of renal disease management in children. We present CPRs for the dietary intake of Ca and P in children with CKD stages 2-5 and on dialysis (CKD2-5D), describing the common Ca- and P-containing foods, the assessment of dietary Ca and P intake, requirements for Ca and P in healthy children and necessary modifications for children with CKD2-5D, and dietary management of hypo- and hypercalcemia and hyperphosphatemia. The statements have been graded, and statements with a low grade or those that are opinion-based must be carefully considered and adapted to individual patient needs based on the clinical judgment of the treating physician and dietitian. These CPRs will be regularly audited and updated by the PRNT.

Can neutral dietary cation-anion difference (DCAD) decrease occurrence of clinical periparturient hypocalcaemia in dairy cattle?

BACKGROUND: Adjusting the dietary cation-anion difference (DCAD) is one of the most efficient ways to stimulate calcium homeostasis in periparturient dairy cattle. However, adjusting DCAD to the recommended negative values (-100 to -150 mEq/kg) is associated with decreased food intake and metabolic acidosis. The critical conditions of the animals at peripartum (i.e. drastic hormonal changes, decreased appetite and negative energy balance) can be detrimental to the health, productivity and welfare of the animals if combined with decreased feed intake caused by unpalatable acidogenic salts. METHODS: In a cross-sectional study, we analysed the ration of eight small to large dairy herds with intensive husbandry systems, including 6949 dry cows. Sodium, potassium, chlorine and sulfur concentrations in the feed were determined and DCAD was calculated. The DCAD of the ration of the farms ranged from -33.5 to +24.7 mEq/kg. Parturient paresis (PP, or milk fever) prevalence was investigated and correlated to DCAD values. RESULTS: Clinical PP occurrence in the dairies of this investigation on average declined by 87% (ranging from a 97% decline to 5% increase). This indicates that adjusting DCAD at neutral values (0 ± 30 mEq/kg range) may both lower the PP prevalence and increase ration palatability by lowering acidogenic salts in the ration. CONCLUSIONS: Further research is recommended to investigate the effects of neutral DCAD on subclinical hypocalcaemia and food intake of the cattle.

Vitamin D deficiency in mothers, neonates and children.

Vitamin D is produced in response to the exposure of skin to sunlight through UV-B synthesis. It can also be obtained from diet and dietary supplements. Vitamin D is essential for strong bones as it helps to absorb calcium from diet. Vitamin D deficiency mainly occurs if strict vegetarian diet is followed as mostly the source of vitamin D is animal based; therefore, exposure to sunlight is restricted or having dark skin color. Low vitamin D levels results in increased possibility of gestational diabetes among pregnant women, low birth weight and pre-eclampsia in infants, and mothers may suffer bone impairment, osteoporosis, hypocalcaemia, and hypertension. Vitamin D deficiency is directly linked with severe complication in mothers and neonates, causing rickets, poor fetal growth and infantile eczema in neonates. Higher prevalence rate of vitamin D deficiency has led professionals to emphasize on development of relevant precautionary measures.

Calcium and magnesium physiology and nutrition in relation to the prevention of milk fever and tetany (dietary management of macrominerals in preventing disease).

Dairy cows may suffer events of hypocalcemia and hypomagnesemia, commonly known as milk fever and tetany. Milk fever is characterized by hypocalcemia at parturition as a consequence of a sudden increase in Ca demand and an unavoidable delay in Ca metabolism adaptation. Tetany is due to impaired Mg absorption from the rumen that cannot be compensated by absorptive or excretory adaptation, resulting in a net nutritional shortage of Mg and culminating in hypomagnesemia. Prevention strategies require triggering the activation of Ca gastrointestinal absorption and avoiding factors limiting ruminal Mg absorption.

Role of postoperative vitamin D and/or calcium routine supplementation in preventing hypocalcemia after thyroidectomy: a systematic review and meta-analysis.

BACKGROUND: Transient hypocalcemia is a frequent complication after total thyroidectomy. Routine postoperative administration of vitamin D and calcium can reduce the incidence of symptomatic postoperative hypocalcemia. We performed a systematic review to assess the effectiveness of this intervention. The primary aim was to evaluate the efficacy of routine postoperative oral calcium and vitamin D supplementation in preventing symptomatic post-thyroidectomy hypocalcemia. The second aim was to draw clear guidelines regarding prophylactic calcium and/or vitamin D therapy for patients after thyroidectomy. METHODS: We identified randomized controlled trials comparing the administration of vitamin D or its metabolites to calcium or no treatment in adult patients after thyroidectomy. The search was performed in PubMed, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Google Scholar, and Web of Knowledge databases. Patients with a history of previous neck surgery, calcium supplementation, or renal impairment were excluded. RESULTS: Nine studies with 2,285 patients were included: 22 in the vitamin D group, 580 in the calcium group, 792 in the vitamin D and calcium group, and 891 in the no intervention group, with symptomatic hypocalcemia incidences of 4.6%, 14%, 14%, and 20.5%, respectively. Subcomparisons demonstrated that the incidences of postoperative hypocalcemia were 10.1% versus 18.8% for calcium versus no intervention and 6.8% versus 25.9% for vitamin D and calcium versus no intervention. The studies showed a significant range of variability in patients' characteristics. CONCLUSIONS: A significant decrease in postoperative hypocalcemia was identified in patients who received routine supplementation of oral calcium or vitamin D. The incidence decreased even more with the combined administration of both supplements. Based on this analysis, we recommend oral calcium for all patients following thyroidectomy, with the addition of vitamin D for high-risk individuals.

A novel model to explain dietary factors affecting hypocalcaemia in dairy cattle.

Most dairy cows exhibit different degrees of hypocalcaemia around calving because the gestational Ca requirements shift to the disproportionately high Ca requirements of lactation. Ca homeostasis is a robust system that effectively adapts to changes in Ca demand or supply. However, these adaptations often are not rapid enough to avoid hypocalcaemia. A delay in the reconfiguration of intestinal Ca absorption and bone resorption is probably the underlying cause of this transient hypocalcaemia. Several dietary factors that affect different aspects of Ca metabolism are known to reduce the incidence of milk fever. The present review describes the interactions between nutrition and Ca homeostasis using observations from cattle and extrapolations from other species and aims to quantitatively model the effects of the nutritional approaches that are used to induce dry cows into an early adaptation of Ca metabolism. The present model suggests that reducing dietary cation-anion difference (DCAD) increases Ca clearance from the blood by dietary induction of systemic acidosis, which results in hypercalciuria due to the loss of function of the renal Ca transient receptor potential vanilloid channel TRPV5. Alternatively, reducing the gastrointestinal availability of Ca by reducing dietary Ca or its nutritional availability will also induce the activation of Ca metabolism to compensate for basal blood Ca clearance. Our model of gastrointestinal Ca availability as well as blood Ca clearance in the transition dairy cow allowed us to conclude that the most common dietary strategies for milk fever prevention may have analogous modes of action that are based on the principle of metabolic adaptation before calving.

Nutritional problems related to food allergy in childhood.

Food allergy is becoming an increasing problem worldwide with an estimated 6-8% of children affected at some point in their childhood. The perceived prevalence of food allergy is even higher with an estimated 20% of children adhering to some form of elimination diet. Against this background, accurate diagnosis is essential to prevent the imposition of unnecessarily restrictive diets on young children. Raising clinical awareness amongst health professionals as to the clinical characteristics, epidemiology, investigation, and management of food allergic disorders is key to tackling this growing problem. In this article, three separate cases of children with poor nutrition and secondary morbidity are presented, highlighting the varying scenarios in which these conditions can be encountered. In the first child, the features clinically displayed were hypocalcemic seizures and rickets due to prolonged breast feeding, poor weaning, and inadequate dietary supplementation. The second case reveals the dangers of complementary diagnostic allergy testing leading to poor nutrition as a consequence of an unsupervised elimination diet. The last report describes a child with multiple food allergies, failure to thrive, and protein losing enteropathy to highlight the diversity of nutritional problems faced by allergists and to underline the importance of specialist dietetic input in the management of a child with food allergy.

Calcium deficiency-induced secondary hyperparathyroidism and osteopenia are rapidly reversible with calcium supplementation in growing rabbit pups.

The reversibility of osteopenia secondary to isolated Ca deficiency (CaDef) is still not clear. We studied the effect of severe CaDef on Ca homeostasis and bone accrual in a 'hypercalcaemic' animal, the rabbit, during the post-weaning period and its reversibility on Ca supplementation. Male Belgian 5-week-old rabbit pups were fed CaDef diet (0.026 % Ca) for 10 weeks. As compared with those fed with a normal chow diet (0.45 % Ca), CaDef pups developed significant hypocalcaemia (P < 0.05), hypocalciuria (urinary Ca 76 (SEM 12) v. 17 (SEM 1) mg/l; P < 0.005), hypophosphataemia (serum inorganic P 100 (SEM 6) v. 65 (SEM 4) mg/l; P < 0.005), secondary hyperparathyroidism (SHPT) (serum intact parathyroid hormone human equivalent 18.2 (SEM 1.4) v. 125.0 (SEM 4.5) pg/ml; P < 0.001) and elevated serum calcitriol levels (34.0 (SEM 3.9) v. 91.0 (SEM 1.0) pg/ml; P < 0.005). Elevated urinary C-terminal telopeptide of class I collagen (P < 0.005) and total serum alkaline phosphatase (P < 0.005) suggested increased bone turnover. There was a significantly lower gain in bone mineral density (BMD) and bone mineral content (BMC) in the whole body and lumbar spine in vivo, and various sub-regions of the femur and tibia in vitro. Supplementation of adequate Ca (0.45 % Ca) after 15 weeks on the normal diet resulted in rapid catch-up growth, and resolution of SHPT. Rapid gain in various BMD and BMC parameters continued at 30 weeks of age, and both were comparable with those in rabbits on a normal diet. We conclude that Ca deficiency-induced SHPT and poor bone accrual in growing rabbit pups are rapidly reversible with Ca supplementation. The present study indicates that early intervention may be a more appropriate window period for human nutritional corrective measures.

Celiac disease manifesting as isolated hypocalcemia.

OBJECTIVE: To describe a patient who presented with hypocalcemia and hypocalciuria as the initial manifestations of celiac disease, despite a normal vitamin D status. METHODS: We review the diagnostic evaluation, treatment, and biochemical and bone mineral density responses of a patient with asymptomatic celiac disease, which was initially suggested because of a low serum calcium level that became attributable to isolated malabsorption of calcium. RESULTS: A 36-year-old woman presented with hypocalcemia in the presence of normal serum 25-hydroxyvitamin D and high serum 1,25-dihydroxyvitamin D levels. She had hypocalciuria and secondary hyperparathyroidism that were refractory to pharmacologic calcium and cholecalciferol supplementation. Fecal calcium excretion indicated malabsorption of calcium, and biopsy of the small intestine demonstrated pathologic changes characteristic of celiac disease. Bone mineral density, determined by dual-energy x-ray absorptiometry, was in the osteopenic range at the femoral neck. The initiation of a gluten-free diet resulted in correction of all biochemical abnormalities and a substantial increase in bone mineral density. CONCLUSION: Primary intestinal malabsorption of calcium without concomitant vitamin D deficiency is possible in celiac disease because of the preferential involvement of the proximal small intestine early in the disease process. Our patient had hypocalcemia caused by celiac disease and values for serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D that were normal and elevated, respectively. Correction was demonstrated after dietary gluten withdrawal.

Presentation of vitamin D deficiency.

AIMS: To describe the various ways in which vitamin D deficiency presents in children in selected districts of London and to identify which factors, if any, determine the mode of presentation. METHODS: Retrospective review of patients presenting to Newham General, Royal London, Great Ormond Street, and King's College Hospitals between 1996 and 2001 with either hypocalcaemia or rickets caused by vitamin D deficiency. Children with plasma 25-hydroxyvitamin D levels <25 nmol/l (10 ng/ml) were considered to have vitamin D deficiency. RESULTS: Sixty five children, mostly from Black or Asian ethnic minority groups, were identified, 29 of whom had hypocalcaemic symptoms. Seventeen of these had no radiological evidence of rickets. The remainder (48 children) had radiological evidence of rickets with or without clinical signs. Symptoms and signs reverted to normal in all cases with vitamin D supplementation. All children who presented with symptomatic hypocalcaemia were aged either <3 or >10 years. There was a strong correlation between age at presentation and population growth velocity reference data. CONCLUSIONS: Rickets remains a problem in the UK especially in "at risk" ethnic minority groups. Symptomatic hypocalcaemia is an important, but under-recognised presenting feature. Growth rate is likely to be an important factor in determining the mode of presentation. Unexplained hypocalcaemia should be attributed to vitamin D deficiency in "at risk" ethnic minority groups until proved otherwise.

Correction of the abnormal mineral ion homeostasis with a high-calcium, high-phosphorus, high-lactose diet rescues the PDDR phenotype of mice deficient for the 25-hydroxyvitamin D-1alpha-hydroxylase (CYP27B1).

Mutations in the 25-hydroxyvitamin D-1alpha-hydroxylase gene (CYP27B1; 1alpha-OHase) cause pseudo vitamin D deficiency rickets (PDDR), while mutations in the vitamin D receptor (VDR) cause hereditary vitamin D resistance rickets. Animal models of both diseases have been engineered. The bone phenotype of VDR-ablated mice can be completely rescued by feeding the animals with a high-calcium, high-phosphorus, high-lactose diet. We have attempted to rescue the PDDR phenotype of mice deficient for the 1alpha-OHase gene by feeding them with the high-calcium diet. The rescue regimen consisted of feeding a diet containing 2% calcium, 1.25% phosphorus, 20% lactose (rescue diet) from 3 weeks of age until sacrifice at 8.5 weeks of age. Blood biochemistry analysis revealed that the rescue diet corrected the hypocalcemia and secondary hyperparathyroidism. Despite the restoration of normocalcemia, 1alpha-OHase(-/-) (and 1alpha-OHase(+/-)) animals fed the rescue diet initially gained weight less rapidly than control mice fed normal mouse chow. Although 1alpha-OHase(-/-) mice fed the rescue diet eventually reached the same weight as control animals, the treatment did not entirely correct bone growth, as femur size remained significantly smaller than that of control. Bone histology and histomorphometry confirmed that the rickets and osteomalacia were cured. The rescue diet also restored the biomechanical properties of the bone tissue within normal parameters. These results demonstrate that correction of the abnormal mineral ion homeostasis by feeding with a high-calcium rescue diet is effective to rescue the PDDR phenotype of 1alpha-OHase mutant mice. This treatment, however, does not appear as effective as 1,25(OH)(2)D(3) replacement therapy since bone growth remained impaired.

Celiac disease as a cause of transient hypocalcemia and hypovitaminosis D in a 13 year-old girl.

We report a thirteen year-old girl with symptomatic hypocalcemia secondary to celiac disease. Serum vitamin D levels [25OH-VitD3 and 24,25(OH)2-VitD3] were low, whereas 1,25(OH)2D3 and PTH levels were higher than normal. Shortly after introducing a gluten-free diet, the patient became asymptomatic, regaining normal growth and pubertal development and serum calcium levels returned to normal.

[The clinical relevance of phosphorus and calcium in infant nutrition]. / Klinische Relevanz des Phosphors und Kalziums in der Säuglingsernährung.

This paper is an introduction to the clinical part of the symposium and deals with the question of whether and under which circumstances the calcium and phosphorus content in baby formula can provoke pathological conditions. In a healthy baby, high or low mineral intake is efficiently compensated for by Ca-P homeostasis. Both nutritional calcium deficiency and calcium excess are the exception with modern baby feeding practices. However, P-deficiency states resulting in phosphopenic rickets might occur in premature babies and in children with familial hypophosphatemic rickets. These two conditions should be treated and prevented by an alimentary P-supplement. On the other hand, formula with a rich P-content might be a cause of the late form of neonatal hypocalcemia. Therefore, a relatively low-phosphate formula preparation, similar to human milk, is recommended for the first 2 weeks of life of full-term newborns, as well for infants with hyperphosphatemic renal failure.

Addition of chloride to a prepartal diet high in cations increases 1,25-dihydroxyvitamin D response to hypocalcemia preventing milk fever.

In this study, we present evidence that cows fed highly cationic diets are less responsive to parathyroid hormone than those fed a highly anionic diet. Forty-seven Jersey cows (55 mo of age) were fed an alfalfa haylage-based diet supplemented with either anions (Cl-) or cations (Na+). Cows fed the high cationic diet suffered significantly more cases of milk fever (6 out of 23) than those fed the high anionic diet (1 out of 24). Concentrations of Ca at parturition and the first 2 d of lactation were significantly higher in cows fed the anionic diet. Secretion of parathyroid hormone in response to developing hypocalcemia was similar in cows fed either diet. Plasma hydroxyproline concentration (an index of bone Ca resorption activity) was greater in cows fed the anionic diet, suggesting better utilization of bone Ca. Plasma 1,25-dihydroxyvitamin D concentration was correlated inversely with plasma Ca and related directly to plasma parathyroid hormone in both groups of cows. However, the magnitude of the response (the amount of 1,25-dihydroxyvitamin D produced per unit increase in parathyroid hormone) was reduced greatly in cows fed the high cation diet. Because parathyroid hormone regulates both bone Ca resorption and renal 1,25-dihydroxyvitamin D production, these data suggest that prepartal diets high in cations decrease the ability of bone and renal tissues to respond to parathyroid hormone. Addition of anions to prepartal diets can reduce the excess cation balance of diets, increasing tissue response to parathyroid hormone and enabling the cow to better adapt to the Ca demands of lactation.

Pseudohipoparatiroidismo y cardiomiopatía hipocalcémica / Pseudohypoparathyroidism an hypocalcemic myocardiopathy

Se presenta un caso de pseudohipoparatiroidismo complicado con una cardiomiopatía hipocalcémica y un síndrome convulsivo. En el momento del diagnóstico, los hechos más destacados fueron: rasgos fenotípicos característicos, cardiomegalia radiológica, alteraciones electrocardiográficas compatibles con hipocalcemia, osteoporosis generalizada y calcificaciones de tejidos blandos en la radiografía de esqueleto, calcio plasmático 4,53 mg% y fosfato plasmático 7,7mg%. En respuesta al tratamiento con vitamina D3, gluconato de calcio, hidróxido de aluminio, acetildigitoxina, hidroclorotiazida, y con un régimen pobre en fosfatos, se obtuvo una mejoría progresiva del calcio y fósforo plamáticos, junto con la normalización de la silueta cardíaca y del trazado electrocardiográfico

Vitamin D metabolites in plasma of cows fed a prepartum low-calcium diet for prevention of parturient hypocalcemia.

Our objective was to characterize changes in vitamin D metabolites of plasma in Jersey cows fed a prepartum low-calcium diet. Eight cows were fed a high-calcium diet (80 g/day) and eight were fed a low-calcium diet (8 g/day) at least 14 days before parturition. Calcium concentrations in plasma decreased after initiation of feeding either diet, but cows fed low-calcium diet tended to have lower prepartum calcium and phosphorus and greater peripartal calcium in plasma. Hydroxyproline in plasma was greater during peripartal period in cows fed low-calcium diet. Prepartum 1,25-dihydroxyvitamin D in plasma tended to be greater in cows fed low calcium. Increases in 1,25-dihydroxyvitamin D were only 2 and 3 days after initiation of the low-calcium diet; during the first 2 days after parturition, however, 1,25-dihydroxyvitamin D tended to be lower in those cows fed low calcium. As parturition neared, 24,25-dihydroxyvitamin D tended to be lower in cows fed the low calcium-diet. Usual early postpartum changes in calcium phosphorus, magnesium, 1,25-dihydroxyvitamin D, and hydroxyproline were seen during first few days after initiation of feeding low calcium. Thus, we propose that the preventative action of the low-calcium diet is associated with preparation of the calcium homeostatic mechanism several days before the calcium demand of initiation of lactation.